Certain peptides are capable of self assembly when incubated in the presence of a low concentration of monovalent metal cation (U.S. Pat. No. 5,670,483; 6,548,630). Assembly results in the formation of a gel-like membrane that is non-toxic, non-immunogenic and relatively stable to proteases. Once formed, membranes are stable in serum, aqueous solutions and cell culture medium. They can be made under sterile conditions, are capable of supporting the growth of cells and are slowly digested when implanted in an animal's body. These characteristics make the membranes well suited as devices for the delivery of therapeutic agents. Among the most promising of such agents is platelet-derived growth factor (PDGF).
PDGF is a mitogen for connective tissue cells, fibroblasts and smooth muscle cells. It has been implicated as contributing to malignant transformation (Clarke, et al., Nature 308:464 (1984); Gazit, et al., Cell 39:89 (1984); Beckmann, et al., Science 241:1346 (1998); Smits, et al., Am. J. Pathol. 140:639 (1992)); and, by promoting the growth of endothelial cells, may contribute to the angiogenesis needed to sustain tumor growth. There is also evidence that PDGF contributes to the restenosis that often occurs after angioplasty (Ferns, et al., Science 253:1129-1132 (1991); Rutherford et al., Atherosclerosis 130:45-51 (1997); Jawien et al. J. Clin. Invest. 89:507-511 (1992)) and to the development of fibrotic lesions in several different organs (Experimental Pharmacology, Peptide Growth Factors and Their Receptors, Sporn & Roberts, eds., pp. 173-262, Springer, Heidelberg).
From a therapeutic perspective, PDGF appears to play a role in promoting the growth of neuronal tissue and in wound healing (Deuel, et al., J. Clin. Invest. 69:1046-1049 (1981); Siegbhan, et. al., J. Clin. Invest. 85:916-920 (1990); Smits, et al., Proc. Natl. Acad. Sci. USA. 88:8159-8163 (1991); Yeh, et al., Cell 64:209-216 (1991); Robson, et al., Lancet 339:23-25 (1992)). There are also indications that PDGF may be used to help preserve cardiac function in patients following a myocardial infarction.